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Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention

Phase 3
45 Years
75 Years
Open (Enrolling by invite only)
Colorectal Adenomatous Polyps

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Trial Information

Calcium/Vitamin D, Biomarkers & Colon Polyp Prevention

Problem of Interest Colon cancer is the second most common cause of cancer death in the
United States, and is the only major cancer to affect both men and women equally. There is
evidence that higher amounts of calcium and vitamin D in the diet may protect against
getting colon cancer, but this has not been tested in human trials until now. Much of the
advance in reducing mortality from heart disease in this country has been related to making
biological measurements (or "biomarkers of risk") on people, such as blood cholesterols.
Such measurements help tell us who is at risk, what they need to do about it, and whether or
not their efforts (diet, lifestyle modification, medications, etc) are being successful. To
date, there have been no such measurements to help cancer prevention efforts. We have
developed a set of biomarkers of risk for colon cancer, and in this study we will test 1)
whether or not calcium and/or vitamin D supplementation can favorably affect these
biomarkers in persons who are at higher than average risk for colon cancer (ie, have already
undergone the removal of colon growths, called adenomatous polyps, which are known to be
precursors to developing colon cancer), and 2) whether effects on the biomarkers predict who
will get new colon polyps or not.

How the Problem Will Be Studied This study will be an add-on study ('adjunct study') to a
'clinical trial' that is currently already being conducted (the 'parent study'). A clinical
trial is a type of study in which participants are randomly assigned to different active or
inactive (placebo) treatments, and measurements of interest are obtained to see if the
active treatment had the desired effect. Our study participants will be composed of persons
who attend the Digestive Diseases Clinic, of the Emory Clinic who have had previous colon
polyps as described above and are already participating in the "Vitamin D/Calcium Polyp
Prevention Study", the parent study. In the parent study, a total of 1,964 people
nationally are being randomly assigned to four different treatment groups: 1) calcium
supplements, 600 mg twice a day; 2) vitamin D supplements, 500 IU twice a day; 3) both the
calcium and vitamin D supplements twice a day; and 4) placebo tablets twice a day. These
amounts are in the upper range of normal dietary intakes of these nutrients. Neither the
participants nor the investigators, except for an emergency, know what treatment anyone is
on until the study is over. The treatment period lasts three to five years at the end of
which study participants undergo a follow-up colonoscopy to look for new polyps. The parent
study has been underway for about a year, and there are already some patients in the trial
who are receiving their study 'treatments' (ie, have been 'randomized'), but more patients
will be recruited into the parent study over the next two years.

Depending on whether someone has already been randomized, they will be invited to
participate in the adjunct study in one of two ways ('Aim 1' only, or 'All Aims'). First,
patients (approximately 124 at Emory) who have already been randomized will be asked to
allow biopsies to be made of their rectal tissue during their 3- or 5-year follow-up
colonoscopy (Aim 1). Biopsies, which will be used for our biomarker measurements, are very
tiny pieces of tissue that can be examined under the microscope. Second, patients
(approximately 100 at Emory) who have not yet been randomized will be invited to participate
more fully (All Aims) in the adjunct study. This involves having outpatient rectal biopsies
taken immediately after their first phone call, their 1-year follow-up visit, and 7 - 21
days before their 3- or 5-year follow-up colonoscopy. These biopsies involve inserting a
tube—about as long and big around as a doctor's examining finger—through the anus into the
rectum or lower colon to a depth of about 3-4 inches. At this spot, 4 - 6 tiny pinches of
tissue one mm thick (less than 1/16 of an inch) will be taken. The procedure takes less
than two minutes, is painless (the only discomfort is like that of having a rectal exam),
and is very low risk—about like having blood drawn. Finally, during their 3- or 5-year
colonoscopy, biopsies will be taken from three areas of the colon: the rectum (same area as
the outpatient biopsies), the sigmoid colon, and the ascending colon. From all of the
biopsies taken from all of the visits and colon sites, biomarker measurements will be of
normal proteins that occur in the surface cells lining the colon. We will then analyze
whether calcium and/or vitamin D affect these biomarkers and whether the effects predict who
gets new polyps.

How the Research Will Advance Scientific Knowledge and/or Human Health Colon cancer is a
very common cancer and there are many factors that play a role in it. By studying the
changes in the lining of the colon, we may be able to select the tests that give the most
information about someone's risk for re-growing colon polyps or developing colon cancer. In
the future, these tests may be used in the general population to identify individuals at
high risk of developing colon cancer, determine what preventive actions need to be taken,
and monitor whether the preventive actions are working well enough, just as we do for blood
cholesterols in efforts to prevent heart attacks.

Also, if we find that calcium or vitamin D, alone or in combination, can favorably affect
these changes in the lining of the colon, it may mean that people will have a simple and
safe way to reduce their chances for re-growing colon polyps or developing colon cancer.

Currently participating in the parent study. Not open to people not already enrolled in
the parent study. This sub-study is for the collection of biopsies only, while the parent
study is for calcium and vitamin D to prevent reoccurrence of colon polyps.

Inclusion Criteria:

- 45 - 75 years old.

- ≥ 1 histologically-verified neoplastic polyps, ≥ 2 mm in diameter, removed from the
large bowel within 4 months of study entry, with entire large bowel examined by
colonoscopy and documented free of further polyps.

- Willing to follow the study protocol, as indicated by the subject's informed consent
to participate.

- Good general health, with no severely debilitating diseases or active malignancy that
might compromise the patient's ability to complete the study.

- Anticipated colonoscopic follow up three years or five years after the qualifying

Exclusion Criteria:

- Invasive carcinoma in any colonic polyp removed.

- Familial colonic polyposis syndromes.

- Ulcerative colitis or Crohn's disease.

- Malabsorption syndrome (e.g., pancreatic insufficiency).

- History of large bowel resection for any reason.

- Diagnosed narcotic or alcohol dependence.

- Elevated serum calcium or creatinine, or supraphysiologic levels of 25(OH) vitamin D
at study entry.

- Current use of thiazide diuretic in amount greater than the equivalent of 50 mg of

- New York Heart Association Cardiovascular Disease functional class 3 or 4.

- On renal dialysis.

- History of kidney stones, unexplained hematuria, or sarcoidosis in the previous 20

- Any history of hypo- or hyperparathyroidism.

- Unwilling to forgo individual calcium and vitamin D supplementation during the trial.

- Unwilling to forgo daily intake of more than a quart of milk (or equivalent in other
dairy products) or daily dietary intake of vitamin D estimated to be greater than 400

- History of osteoporosis or other medical condition that may require supplemental
calcium or vitamin D.

- Current use of bisphosphonates (eg, alendronate [Fosamax], risendronate [Actonel]).

- Current use of calcitonins (eg, Miacalcin).

Additional exclusion criteria for the adjunct biomarker study are:

- Unable to be off aspirin for 7 days.

- History of bleeding disorder or current use of anticoagulant medication.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Outcome Measure:

Biomarkers of Risk for Colorectal Neoplasms

Outcome Description:

Molecular phenotyping of a panel of putative biomarkers of risk for colorectal neoplasms in the normal appearing colorectal epithelium: COX-2, APC, β-catenin, E-cadherin, MLH1, telomerase, bcl-2, bax, TGFα, TGFβ1

Outcome Time Frame:

1 year and 3 or 5 years

Safety Issue:


Principal Investigator

Roberd M Bostick, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University


United States: Institutional Review Board

Study ID:




Start Date:

June 2006

Completion Date:

September 2018

Related Keywords:

  • Colorectal Adenomatous Polyps
  • colonic neoplasms
  • colorectal adenoma
  • calcium
  • vitamin D
  • Colonic Polyps
  • Polyps
  • Adenomatous Polyps



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